Effect of Statins on Pathobiology of Alzheimer's Disease

描述(申请人提供)：候选人：卡尔松博士的长期目标是成为阿尔茨海默病(AD)及其与血管风险因素的关系的独立临床研究员。作为K23奖项的一部分，Carlsson博士将通过华盛顿大学人口健康科学理学硕士项目、华盛顿大学研究生院心理学系和临床研究基础凯斯顿证书计划，在临床研究设计、生物统计学、认知理论和测试、流行病学和数据管理方面获得高级培训，从而在以患者为导向的研究领域发展自己的职业生涯。此外，她将通过临床研究员预备课程(CIPP，NIH K30)完成培训。她还将接受管理人类受试者研究的伦理和监管问题方面的高级培训。环境：威斯康星大学医学院是一家主要的研究机构，最近将老年病学和神经科学确定为五大优先研究领域中的两个。除了威斯康星州记忆研究计划和老年病学和老年病学分部，卡尔松博士还将获得拟议的K23奖项的下列资源：威斯康星州阿尔茨海默氏症研究所、威斯康星州阿尔茨海默氏症预防登记处、老龄研究所、退伍军人事务部老年研究、教育和临床中心(GRECC)以及综合临床研究中心(GCRC)。研究：鉴于流行病学、动物和临床研究的证据表明他汀类药物可能对AD具有预防作用，Carlsson博士建议评估辛伐他汀对AD进展的脑脊液(CSF)和血浆标记物、中枢神经系统(CNS)胆固醇代谢和CNS炎症的影响。来自威斯康星州阿尔茨海默病预防登记处的100名非痴呆症男性和女性将被招募参加一项为期9个月的随机对照试验，评估辛伐他汀每晚80毫克与安慰剂相比对1)脑脊液淀粉样β-42(Abeta42)水平的影响；2)中枢神经系统胆固醇代谢的血浆标记物；以及3)脑脊液和血浆炎症标记物的影响。参与者将在基线和9个月的随访中抽出空腹实验室，收集脑脊液，并进行认知测试。在1个月、3个月和6个月的额外检查将评估副作用。认知测试也将在3个月的随访中重复进行。9个月时的结果测量将与基线进行比较。结果将通过载脂蛋白E4状态进行分析。

DESCRIPTION (provided by applicant): Candidate: Dr. Carlsson's long-term goal is to become an independent clinical investigator in Alzheimer's disease (AD) and its relationship to vascular risk factors. As part of this K23 award, Dr. Carlsson will develop a career in patient-oriented research by obtaining advanced training in clinical research design, biostatistics, cognitive theory and testing, epidemiology, and data management through the UW Masters of Science in Population Health Sciences Program, the UW Graduate School Department of Psychology, and the Capstone Certificate Program in Fundamentals of Clinical Research. Furthermore, she will complete her training through the Clinical Investigator Preparatory Pathway (CIPP, NIH K30). She will also obtain advanced training in ethical and regulatory issues that govern human subjects research. Environment: The University of Wisconsin Medical School is a premier research institution that has recently identified Geriatrics and Neurosciences as two of the top five priority areas for research. In addition to the UW Memory Research Program and Section of Geriatrics and Gerontology, Dr. Carlsson will have access to the following resources for the proposed K23 award: the Wisconsin Alzheimer's Institute; the Wisconsin Registry for Alzheimer's Prevention; the Institute on Aging; the VA Geriatric Research, Education and Clinical Center (GRECC); and the General Clinical Research Center (GCRC). Research: Given the evidence from epidemiological, animal, and clinical research suggesting that statins may have a preventive role in AD, Dr. Carlsson proposes to evaluate the effect of simvastatin on cerebrospinal fluid (CSF) and plasma markers of AD progression, central nervous system (CNS) cholesterol metabolism, and CNS inflammation in a population of middle-aged adults at increased risk for developing AD. 100 men and women without dementia from the Wisconsin Registry for Alzheimer's Prevention will be recruited for participation in a 9-month randomized, controlled trial evaluating the effects of simvastatin 80 mg nightly vs. placebo on 1) CSF amyloid beta-42 (Abeta42) levels; 2) plasma markers of CNS cholesterol metabolism; and 3) CSF and plasma markers of inflammation. Participants will have fasting labs drawn, CSF collected, and cognitive testing done at baseline and 9-month follow-up. Additional visits at 1, 3, and 6 months will assess side effects. Cognitive testing will also be repeated at the 3-month follow-up. Outcome measures at 9 months will be compared to baseline. Results will be analyzed by apolipoprotein E4 status.